ZIC2 promotes colorectal cancer growth and metastasis through the TGF-β signaling pathway

Shi, Zhehao; Bao, Wenming; Zheng, Jiuyi; Chen, Kaiyu; Lin, Ziyuan; Song, Hao-Nan; Luo, Xin; Dong, Qian-Tong; Jiang, Lei; Wang, Yi; Chen, Gang; Chen, Xiaolei

doi:10.1016/j.yexcr.2022.113118

Cited by 13 publications

(6 citation statements)

References 32 publications

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“…In CRC, MMP1 derived from tumor-associated macrophages promotes the cell cycle transition from G0/G1 to S and G2/M phases [ 49 ], and the overexpression of HOXC6 induces EMT in colon cancer cells [ 50 ]. ZIC2 and SFTA2 may be identified as critical genes in CRC carcinogenesis [ 51 , 52 ]. Furthermore, HYAL1 inhibits CRC metastasis by modulating MMPs/TIMPs balance and rearranging F-Actin distribution [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer

Man,

Xin,

et al. 2024

Discov Onc

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Background and objectives Colorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature. Methods CRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature. Results From the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients. Conclusion MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer

Man,

Xin,

et al. 2024

Discov Onc

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“…Cofilin 13 was translocated in the mitochondrial fraction after treatment with TGF‐β1 41 . ZIC2 8 promoted colorectal cancer growth and metastasis through the TGF‐β signaling pathway 42 . BAMBI 9 inhibited TGF‐β signaling as a dominant‐negative, non‐signaling, pseudoreceptor for the TGF‐β type I receptor family 43 .…”

Section: Discussionmentioning

confidence: 99%

Combination of high anti‐SKI and low anti‐TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma

Ito,

Yajima,

Suzuki

et al. 2024

Cancer Science

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Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto‐oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti‐SKI antibody (s‐SKI‐Ab) and anti‐TMED5 antibody (s‐TMED5‐Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s‐SKI‐Abs and s‐TMED5‐Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s‐SKI‐Ab‐positive and s‐TMED5‐Ab‐negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s‐SKI‐Ab‐positive and s‐TMED5‐Ab‐negative cases showed an even clearer difference in overall survival as compared with that of s‐SKI‐Ab‐negative and s‐TMED5‐Ab‐positive cases. The s‐SKI‐Ab and s‐TMED5‐Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.

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“…The downstream regulation mechanism of ZIC2 has also been reported. ZIC2 can activate TGF-β, Src/FAK, Notch, Raf/MEK/ERK, and Wnt/β-catenin signaling pathway in colorectal cancer, non-small cell lung cancer, endometrial cancer, liver cancer, and ccRCC cells [28,[35][36][37][38][39]. ZIC2 can transcriptional regulates Src, lncRNA SNHG12, Axin2, Runx2, OCT4, STAT3, PAK4 expression in non-small cell lung cancer, endometrial cancer, colon cancer, ccRCC, lung adenocarcinoma, liver cancer, and breast cancer [15,28,[36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

FOXM1-regulated ZIC2 promotes the malignant phenotype of renal clear cell carcinoma by activating UBE2C/mTOR signaling pathway

Lv¹,

Wang²,

Hou³

et al. 2023

Int. J. Biol. Sci.

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Background: As a transcription factor, Zic family member 2 (ZIC2) has been involved in more and more studies of tumorigenesis, which has been proved by our research team to be an effective prognostic marker for Pan-cancer. However, the prognosis, tumor promoting effect and regulatory mechanism of ZIC2 in clear cell renal cell carcinoma (ccRCC) are still unknown. Methods: The potential clinical significance of ZIC2 was evaluated by bioinformatics analysis using data from TCGA, GEO, and ArrayExpress data sets. WB and IHC were used to detect ZIC2 expression in tumors and adjacent tissues. CCK-8, EdU, colony formation, cell cycle, wound healing, transwell, subcutaneous xenograft, and lung metastasis models were used to detect the biological function of ZIC2. The regulatory mechanism of ZIC2 was confirmed by data of RNA-seq, ATAC-seq, MS-PCR, Chip-PCR, and luciferase reporter experiments. Results: ZIC2 was markedly upregulated and correlated with poor clinicopathological features in ccRCC. Knockdown of ZIC2 resulted in reduced cell proliferation, invasion, migration, induction of G2/M phase arrest, and reduced tumor formation and lung metastasis in nude mice. The opposite was observed after overexpression. Mechanistically, the high expression of ZIC2 is regulated by hypomethylation and high H3K4Me3 in the promoter region, as well as positive transcriptional regulation by FOXM1. And then, ZIC2 transcriptase-positively regulates UBE2C and activates AKT/mTOR signaling pathway to promote tumor malignant progression. Conclusion: This study reveals that FOXM1-ZIC2-UBE2C-mTOR signaling axis promotes the progression of ccRCC, which can be used as a prognostic indicator and potential therapeutic target.

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ZIC2 promotes colorectal cancer growth and metastasis through the TGF-β signaling pathway

Cited by 13 publications

References 32 publications

Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer

Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer

Combination of high anti‐SKI and low anti‐TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma

FOXM1-regulated ZIC2 promotes the malignant phenotype of renal clear cell carcinoma by activating UBE2C/mTOR signaling pathway

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